Discussion
Here we describe interaction of Plasmodium and a Flavivirus in
the recurrence of mortality little less than a decade after emergence of
BAGV in red-legged partridges in Southern Spain. Flaviviruses andPlasmodium share the same mosquito vectors and coinfections of
mosquitoes with Plasmodium and WNV have been described (Medeiros
et al., 2016). Coinfections with Plasmodium have been detected in
passerines from USUV related bird mortalities in the Netherlands and
Belgium and USUV related lesions have recently been described to be more
severe and mortality higher in passerines carrying malaria parasites
(Giglia et al., 2020; Rijks et al., 2016; Rouffaer et al., 2018).This suggests that interactions between malaria parasites and
Flaviviruses may influence the transmission dynamics and host pathogen
interaction of these emerging pathogens (Hughes et al., 2010; Medeiros
et al., 2014), but the relation and type of interactions between both
pathogens in bird-feeding mosquitoes and in their avian hosts are
unclear and information available to date is conflicting. In a study
involving adult North American passerines coinfection withPlasmodium had a negative effect on WNV serostatus (Medeiros et
al., 2014), while in a recent study in Spain WNV serostatus was not
affected by concurrent Plasmodium infection (Ferraguti et al.,
2021). A recent extensive study in Germany documented WNV and USUV
coinfections but did not test for Plasmodium or other avian malaria
parasites (Santos et al., 2021). As for vectors, mosquitoes infected
with BAGV had reduced Japanese encephalitis (JEV) and WNV replication
(Sudeep et al., 2015), but we are not aware of studies on concurrent
infections with Plasmodium .
The BAGV sequences detected in this case differ from the BAGV detected
in the first outbreak caused by this virus (Figure 2), while thePlasmodium sequences detected in the affected birds are identical
and homologous to a sequence detected in biting midges and birds in the
nearby Doñana National Park (Ferraguti et al., 2013). The detection of
this particular genotype in midges, may be of interest, although we do
not at this point have information on the importance of this fact. Also,
previous studies on Plasmodium in red-legged partridges suggest
that in a given population a number of Plasmodium lineages
co-circulate and that Plasmodium prevalence as well as presence
of generalist Plasmodium lineages may be influenced by releases
of farm-reared partridges (García et al., 2021). Avian malaria parasites
are strictly vector bound and suspected to manipulate the biting
behavior of their vectors in order to enhance transmission (Cornet et
al., 2013), which could in the case of co-circulation in the same vector
have an impact on transmission dynamics of locally circulating
Flaviviruses such as BAGV. However, for BAGV in addition to
mosquito-vector transmission, in red-legged partridges direct
transmission has been demonstrated experimentally (Llorente et al.,
2015), which suggests some degree of concurrent direct transmission at
feeders in the case of highly managed populations in hunting estates.
While BAGV is pathogenic in red-legged partridges, avian malaria
parasites are widespread and in Europe generally considered of little
pathogenicity to avian hosts. However, especially Plasmodium spp.
has led to local extinction of island endemic species when introduced
with Eurasian birds to naïve populations and has also recently been
suggested as one of the causes of the decline of abundant Eurasian birds
such as the house sparrow (Passer domesticus ) (Dadam et al.,
2019) and found associated to passerine mortalities in Austria (Dinhopl
et al., 2015). Here mortality seemed to be mediated by the interaction
of both pathogens. Potentially infection of previously Plasmodiuminfected partridges with BAGV and enhanced direct transmission due to
aggregation at feeders and watering points could have led to the
observed mortality. The ecoepidemiology and pathogenesis of this
interaction in red-legged partridges and why this species seems to be
especially susceptible, is unclear and needs further investigation.
Red-legged partridges are both a key species in Mediterranean ecosystems
and, through the gamebird industry, an economic motor for depopulated
regions in southern Spain (Caro et al., 2014; Casas et al., 2016).
Mortality due to BAGV in the 2010 outbreak had a serious impact on the
abundance of natural populations of the species and for the small game
hunting sector (García-Bocanegra et al., 2013), thus reappearance of
BAGV mediated mortality is of concern. More so as zoonotic potential of
this virus has been discussed based upon detection of neutralizing
antibodies against BAGV in patients with Meningoencephalitis in India
(Bondre et al., 2009). Finally, this outbreak evidences the potential of
interaction of co-circulating Plasmodium spp. and Flaviviruses,
and as both groups harbor human pathogens the potential public health
threat that such interaction could encompass should not be neglected.